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Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival

Author

Listed:
  • Martin Schwickart

    (Department of Physiological Chemistry,)

  • XiaoDong Huang

    (Department of Physiological Chemistry,)

  • Jennie R. Lill

    (Department of Protein Chemistry,)

  • Jinfeng Liu

    (Department of Bioinformatics,)

  • Ronald Ferrando

    (Department of Pathology,)

  • Dorothy M. French

    (Department of Pathology,)

  • Heather Maecker

    (Department of Translational Oncology,)

  • Karen O’Rourke

    (Department of Physiological Chemistry,)

  • Fernando Bazan

    (Department of Protein Engineering,)

  • Jeffrey Eastham-Anderson

    (Department of Pathology,)

  • Peng Yue

    (Department of Bioinformatics,)

  • David Dornan

    (Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA)

  • David C. S. Huang

    (The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia)

  • Vishva M. Dixit

    (Department of Physiological Chemistry,)

Abstract

Deubiquitinase USP9X stabilizes MCLl The induced myeloid leukaemia cell-differentiation protein MCL1 is often overexpressed in tumours, where it promotes cancer cell survival. Schwickart et al. now show that the deubiquitinase USP9X stabilizes MCLl and is itself often overexpressed in cancer. In multiple myelomas, higher levels of USP9X are associated with poorer prognosis. RNAi knockdown of USP9X in human embryonic kidney 293 cells promotes MCLl degradation and sensitizes cells to anticancer compounds that induce apoptosis, suggesting that targeting USP9X may represent a novel therapeutic strategy for tumours with MCLl overexpression.

Suggested Citation

  • Martin Schwickart & XiaoDong Huang & Jennie R. Lill & Jinfeng Liu & Ronald Ferrando & Dorothy M. French & Heather Maecker & Karen O’Rourke & Fernando Bazan & Jeffrey Eastham-Anderson & Peng Yue & Davi, 2010. "Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival," Nature, Nature, vol. 463(7277), pages 103-107, January.
    • Handle: RePEc:nat:nature:v:463:y:2010:i:7277:d:10.1038_nature08646
    DOI: 10.1038/nature08646
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    Cited by:

    1. Han Koo & Kyung Chan Park & Hyun Ahm Sohn & Minho Kang & Dong Joon Kim & Zee-Yong Park & Sehoon Park & Sang Hyun Min & Seong-Hwan Park & Yeon-Mi You & Yohan Han & Bo-Kyung Kim & Chul-Ho Lee & Yeon-Soo, 2025. "Anti-proteolytic regulation of KRAS by USP9X/NDRG3 in KRAS-driven cancer development," Nature Communications, Nature, vol. 16(1), pages 1-17, December.

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